| Summary: | 碩士 === 慈濟大學 === 藥理暨毒理學研究所 === 96 === Baicalein is a major bioactive flavonoid component of Scutellaria baicalensis exerting anticancer activity, although the mechanisms are not fully understood. The AKT signaling pathway plays an important role in the regulation of cancer cell proliferation and survival. Securin, also known as pituitary tumour transforming gene (PTTG), is highly expressed in various cancer cells and regulates cancer cell proliferation. In this study, we investigated the role and regulation of AKT and securin on the baicalein-induced cell death in human cancer cells. Baicalein induced cytotoxicity in a variety of human cancer cell lines including bladder, breast, cervical, colon, and lung cancers. Interestingly, baicalein induced the protein phosphorylation of AKT in human cancer cells; however, the securin protein expression was reduced by baicalein. Blockade of AKT pathway by wortmannin or AKT shRNA increased cytotoxicity in the baicalein-treated cells. The securin-wild type cancer cells were more susceptible on the cytotoxicity than the securin-null cancer cells after treatment with baicalein. Baicalein induced the protein phosphorylation of H2AX at Ser 139 (��-H2AX). Furthermore, the protein phosphorylations of AKT and H2AX were increased by baicalein in both the securin-wild type and -null cancer cells. Transfection of H2AX siRNA decreased the ��-H2AX proteins but did not alter the protein levels of phospho-AKT, total AKT, and securin in the baicalein-treated cells. In addition, H2AX siRNA increased the baicalein-induced cytotoxicity in cancer cells. Moreover, wortmannin decreased the protein levels of phospho-AKT and ��-H2AX but did not alter securin protein expression in the baicalein-treated cells. Together, we suggest that inhibition of AKT/��-H2AX pathway may increase the baicalein-induced cytotoxicity, and the existence of securin promotes the baicalein-induced cancer cell death.
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